Prognostic Role of Serum Levels of Uric Acid in Amyotrophic Lateral Sclerosis

Abstract

Background and PurposeIt has been suggested that oxidative stress is one of the pathomechanisms underlying amyotrophic lateral sclerosis (ALS), and thus antioxidants such as uric acid (UA) that could reduce oxidative stress might be beneficial in the prevention or treatment of this disease. The objective of this study was to prospectively investigate serum UA levels in Korean ALS patients and to relate them to disease progression.MethodsALS patients and healthy controls who were individually well-matched for sex, age, and body mass index (BMI) underwent blood testing for serum UA levels, and analyzed whether UA levels were correlated with the disease status of the patients, as defined by the ALS Functional Rating Scale-Revised (ALSFRS-R).ResultsThe study included 136 ALS patients and 136 matched controls. The UA level was lower in the ALS patients (4.50±1.17 mg/dL, mean±SD) than in the controls (5.51±1.22 mg/dL; p<0.001). Among the ALS patients, the level of UA acid was inversely correlated with the rate of disease progression (decrease in ALSFRS-R score). Kaplan-Meier analysis revealed that a better survival rate was more strongly correlated with top-tertile levels of serum UA than with bottom-tertile levels (log-rank test: p=0.035).ConclusionsALS patients had lower serum UA levels than did healthy individuals. UA levels in ALS were negatively correlated with the rate of disease progression and positively associated with survival, suggesting that UA levels contribute to the progression of ALS. UA levels could be considered a biomarker of disease progression in the early phase in ALS patients.

Urate levels predict survival in amyotrophic lateral sclerosis: Analysis of the expanded Pooled Resource Open‐Access ALS clinical trials database

“…Our pooled analysis provides additional support for urate as a predictor of ALS outcomes. Urate has been proposed as a prognostic factor for ALS by some, but not all, authors . Here we leveraged the expansion of PRO‐ACT, the largest aggregation of ALS clinical trials, to examine relationships among urate levels at study entry, survival, and functional decline.…”

“…Urate has been proposed as a prognostic factor for ALS by some, but not all, authors. [32][33][34][35][36][37] Here we leveraged the expansion of PRO-ACT, the largest aggregation of ALS clinical trials, to examine relationships among urate levels at study entry, survival, and functional decline. Our results showing a small but significant association between urate and ALS outcomes are consistent with a growing literature supporting urate as a prognostic and potential neuroprotective agent in neurologic disease.…”

“…More recently, urate levels have been suggested to represent a prognostic factor for ALS survival . However, previous studies in ALS cohorts ranging in size from 86 to 942 participants have reported conflicting results …”

“…31 However, previous studies in ALS cohorts ranging in size from 86 to 942 participants have reported conflicting results. [32][33][34][35][36][37][38][39] The recent development of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database has allowed the analysis of aggregate data from multiple independent ALS clinical trials. 40 Initial analyses have suggested that urate, creatinine, and body mass index (BMI) are all strong predictors of ALS prognosis.…”

Further development of biomarkers in amyotrophic lateral sclerosis

“…Uric acid [99][100] and serotonin [101] were associated with risk of death. Small metabolites evaluated by metabolomics approaches [102][103][104] were linked to phenotypic or genetic characteristics.…”